Population-Based Assessment of Familial Clustering of Diabetic Nephropathy in Type 1 Diabetes

We determined the magnitude of familial aggregation in the development of diabetic nephropathy (DN) among a population-based cohort of Finnish type 1 diabetic patients. Probands with type 1 diabetes were identified from the nationwide register of all Finnish cases diagnosed during 1965-1979. By 1998, there were 537 families with at least two siblings with type 1 diabetes. These 537 probands and their 616 diabetic siblings were followed for a diagnosis of DN until the end of 2001. We identified 323 cases of DN in these families. If the proband had DN, 38% of the siblings also had DN, whereas out of the diabetic siblings of the probands without DN, only 17% had DN (P = 0.001). Diabetic siblings of the nephropathic probands had a 2.3 times (95% CI 1.4-2.7) higher risk of DN compared with siblings of probands free of DN. The presence of a severe form of DN in the proband increases the risk threefold for diabetic siblings. Sex, the DN of the proband, the age at the onset of diabetes, and parental type 2 diabetes were significant predictors of DN among diabetic siblings. Although the majority of sibpairs with type 1 diabetes are discordant for DN, its presence in one sibling doubles the risk for the other diabetic siblings.